The effect of GABAergic neurotransmission on the seizure-related activity of the laterodorsal thalamic nuclei and the somatosensory cortex in a genetic model of absence epilepsy

The present study aimed to investigate the alterations of the GABAergic system in the laterodorsal nucleus (LDN) of the thalamus and the somatosensory cortex (SC) in an experimental model of absence seizure. The effects of pharmacological manipulation of both GABA(A) and GABA(B) receptor subunits in the LDN on the generation of spike-wave discharges (SWD) were evaluated. The experiments were carried out in four groups of both WAG/Rij and Wistar rats with 2 and 6 months of age. The expressions of various GABA receptor subunits were studied in the LDN and SC. Furthermore, recordings of unit activity from the LDN and electrocorticography were simultaneously monitored before, during, and after the application of GABA(A) and GABA(B) antagonists in the LDN. The generation of SWD in the older WAG/Rij rats was associated with significant alterations in the expression of GABA(A)R alpha 1, GABA(A)R beta 3, and GABA(B)R2 subunits in the LDN as well as GABA(A)R alpha 1, GABA(A)RP beta, GABA(A)R gamma 2, and GABA(B)R2 subunits in the SC. Furthermore, the occurrence of SWD was associated with a significant reduction of gene expression of GABA(A)R alpha 1 and increase of GABA(A)R beta 3 in the LDN as well as reduction of GABA(A)R alpha 1, GABA(A)R beta 3, GABA(A)R gamma 3, and GABABR2 in the SC. The microionthophoretic application of the GABA(A) antagonist bicuculline resulted in a significant increase in the population firing rate of LDN neurons as well as the mean number and duration of SWD. The application of the GABA(B) antagonist CGP35348 significantly increased the population firing rate of LDN neurons but decreased the mean number of SWD. Our data indicate the regulatory effect of the GABAergic system of the LDN and SC in absence seizures.

Automated summary

The study investigated alterations of the GABAergic system in the LDN and SC in an experimental model of absence seizure. Results showed changes in GABA receptor subunit expressions in the LDN and SC were associated with the occurrence of SWD. Pharmacological manipulations of GABA receptors in the LDN had varying effects on SWD generation.